Sudden cardiac death remains an outstanding problem despite major advances in the field of acute coronary care. It is likely that a significant number of these untimely deaths could be prevented by adequate pharmacologic therapy. Presently available antiarrhythmic drugs are either ineffective in preventing sudden cardiac death (ventricular fibrillation) or prove to be too toxic when administered on a chronic basis. Our goals for the next 5 years are to continue attempts to develop and evaluate in the experimental animal, agents that specifically protect the ischemic heart against the development of arrhythmias and/or ventricular fibrillation. To meet this objective it will be necessary to develop an animal model of sudden cardiac death. Some success has been achieved in this area and we propose to evaluate our model further and to begin the testing of currently available anti-arrhythmic drugs as well as those developed in our Medicinal Chemistry Laboratories. The electrophysiologic effects and distribution of antiarrhythmic and/or antifibrillatory agents will be studied in normal and ischemic heart muscle to determine if the drugs in question show a selective concentration in jeopardized, electrically unstable myocardium. Through this approach it is our hope that a pharmacologic agent with minimal toxicity can be developed and be useful in protecting patients with ischemic heart disease from ventricular fibrillation or sudden cardiac death.